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Biomedical subjects

Y Kitagawa

Publications and source records attributed to Y Kitagawa.

At least 109 records · Page 6Linked to original sources
PubMed2000

[Laparoscopic surgery for esophageal achalasia].

Laparoscopic surgery for esophageal achalasia was first reported by Shimi et al. in 1991. Subsequently the procedure has been performed all over the world and laparoscopic Heller myotomy and Dor fundoplication (Heller and Dor operation) is now thought to be the operation of first choice. It is indicated for patients who are resistant to medical therapy (calcium blocker etc.) or have pneumatic dilatation and those with frequent aspiration at night. As Csendes et al. reported that surgical treatment was better than pneumatic dilatation and as laparoscopic surgery is less invasive, the indications for the laparoscopic Heller and Dor operation can include all achalasia patients except those who respond to medical therapy, do not accept surgery, or cannot tolerate surgery. We successfully performed the laparoscopic Heller and Dor operation on 22 patients, all of whom had an uneventful postoperative course. Manometric evaluation, endoscopic examination, and 24-hour pH monitoring showed good results. There are six important technical points: 1) flexible laparoscopy; 2) pneumoperitoneum; 3) gauze in the abdominal cavity to absorb blood; 4) laparosonic coagulating shears; 5) extracorporeal knot-tying technique; and 6) intracorporeal knot-tying technique. If an experienced surgeon is in charge, the laparoscopic Heller and Dor operation is an ideal, minimally invasive treatment for esophageal achalasia.

Esophageal Achalasia↗
PubMed2000

Demethylating reagent 5-azacytidine inhibits telomerase activity in human prostate cancer cells through transcriptional repression of hTERT.

Telomerase activation is thought to be a critical step in cellular immortality and oncogenesis. Several reagents including differentiation-inducing and antineoplastic agents are known to inhibit telomerase activity, although the molecular mechanisms through which they inhibit telomerase activity remain unclear. Demethylating reagents have recently been used as potential antineoplastic drugs for some types of cancers including those of the prostate. In the present study, we examined the effect of the demethylating reagent 5-azacytidine (5-aza-CR) on telomerase activity using cells of two prostate cancer cell lines, DU-145 and TSU-PR1. 5-aza-CR treatment significantly reduced telomerase activity in TSU-PR1 cells, but not in DU-145 cells, although growth inhibition was observed to a similar extent in both cell lines. Reverse transcription-PCR analyses revealed that inhibition of telomerase activity was accompanied by down-regulation of telomerase catalytic subunit (hTERT) mRNA expression. Transient expression assays showed that 5-aza-CR repressed the transcriptional activity of the hTERT promoter and that the E-box within the core promoter was responsible for this down-regulation. Western blot analyses revealed that 5-aza-CR reactivated p16 expression and repressed c-Myc expression in TSU-PR1 cells but not in DU-145 cells. Overexpression of p16 in TSU-PR1 cells led to significant repression of c-Myc transcription. These findings suggest that 5-aza-CR inhibits telomerase activity via transcriptional repression of hTERT, in which p16 and c-Myc may play a key role.

Azacitidine↗
PubMed2000

[Temporal arteritis].

Explore the source record for details and available documents.

Central Nervous System Diseases↗
PubMed1999

Analysis of the RNA recognition motifs of human neuronal ELAV-like proteins in binding to a cytokine mRNA.

Human neuronal Elav-like proteins contain three RNP-type RNA recognition motifs (RRMs). Previous reports demonstrated that a single RRM of the proteins is not sufficient to bind to the uridine-rich stretch in the 3' untranslated region of mRNAs and that the bi-RRM peptide consisting of the first two RRMs is necessary for the binding. The present study was designed to examine the potential contributions of the first two RRMs when binding to a cytokine mRNA. Deletions of the internal or terminal amino acid residues of the first RRM (RRM1) of the HuC/ple21 ELAV-like protein completely abolished RNA binding. However, removal of any region of the second RRM (RRM2) except for the eight amino acid residues, which correspond to the potent fourth beta-sheet structure of RRM2, did not affect RNA binding. Conjugation of the eight amino acid residues to RRM1 enhanced the RNA binding as well as the entire RRM2, indicating that the octapeptide of RRM2 can be compensated for by the binding function of RRM2. The present study also showed that the substitutions of glutamic acid at 42 for aspartic acid and leucine at 44 for phenylalanine in the first potent alpha-helix structure of RRM1, as were seen in another ELAV-like protein Hel-N1, markedly affected the RNA binding.

3' Untranslated Regions↗
PubMed1999

Binding of neuronal ELAV-like proteins to the uridine-rich sequence in the 3'-untranslated region of tumor necrosis factor-alpha messenger RNA.

Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that is involved in the pathogenesis of several human CNS disorders. The AU-rich element (ARE) in the 3'-untranslated region (UTR) of TNF-alpha mRNA is implicated in post-transcriptional control of TNF-alpha. In this study, we showed that a human neuronal ELAV-like protein binds to the ARE in the 3'-UTR of TNF-alpha mRNA. The protein binds to the uridine stretch in AUUUA pentanucleotides inside the ARE in the 3'-UTR of TNF-alpha mRNA. The TNF-alpha mRNA-binding region in the protein appears to be identical to the c-myc and IL-3 mRNA-binding regions. Moreover, this study showed that in vitro treatment of neuroblastoma cells with interleukin-4 (IL-4), which inhibits TNF-alpha production, reduced the expression of the neuronal ELAV-like proteins. These results suggest that the expression of neuronal ELAV-like proteins may be closely associated with the expression of TNF-alpha in neuronal cells.

3' Untranslated Regions↗
PubMed1999

A PEA3 site flanked by SP1, SP4, and GATA sites positively regulates the differentiation-dependent expression of Brachyury in embryonal carcinoma P19 cells.

The promoter sequence of Brachyury was analyzed in mouse embryonal carcinoma P19 cells. The sequence up to -267 bp relative to the transcription start site was sufficient to enhance reporter gene expression depending on the mesodermal differentiation of P19 cells. Footprint analysis by nuclear extract showed binding of a GATA protein and SP4 and mutation of their sites reduced reporter gene expression. Gel-retardation assay in the presence of a series of double-stranded DNA fragments as the competitors showed SP1 and Est sites additionally. Deletion of either sites reduced the reporter gene expression, showing that they are cooperative. Depletion of PEA3 (a transcription factor of the Est family) with a specific antibody diminished the retarded bands only for the nuclear extract from differentiated P19 cells. Thus, the PEA3 site supported by SP1, SP4, and GATA sites positively regulates the differentiation-dependent expression of Brachyury in P19 cells.

Animals↗
PubMed1999

Antibody recognition and RNA binding of a neuronal nuclear autoantigen associated with paraneoplastic neurological syndromes and small cell lung carcinoma.

The PLE21/HuC neural protein is an autoantigen for anti-neuronal nuclear autoantibodies (ANNA-1/anti-Hu/Type IIa antibodies) from a patient with paraneoplastic limbic encephalomyelitis and small cell lung carcinoma. This antigen belongs to the Hu/ELAV-like protein family, contains three RNA recognition motifs (RRMs) and has RNA binding capacity. In many autoimmune diseases mediated by autoantibodies, antibodies often interfere with the biological functions of their target antigens. To investigate the influences of the autoantibodies on the biological function of the antigen, we mapped the regions which were required for the antibody recognition and for the RNA binding. Deletion analysis of the antigen revealed that the epitopes for the antibodies were localized in the regions of 12 residues, amino acids 161-172, and eight residues, amino acids 29-38, of the first and second RRMs. It was also shown that the eight residues, amino acids 29-38, and the 10 residues, amino acids 187-194, were required for the RNA binding. Although amino acids 29-38 were necessary for both the antibody recognition and the RNA bindings, pre-incubation of the PLE21 antigen with the antibodies did not inhibit the formation of the complex of PLE21, the antibodies and RNA. Thus, the regions required for the antibody recognition are not identical with those for the RNA binding, and it seems unlikely that the autoantibodies interfere with RNA binding of the antigen.

3' Untranslated Regions↗
PubMed1999

Genetic contribution of the BAT2 gene microsatellite polymorphism to the age-at-onset of insulin-dependent diabetes mellitus.

The BAT2 gene lies within the class III region of the major histocompatibility complex. We investigated the frequency of the BAT2 microsatellite alleles (BAT2) in 74 young-onset insulin-dependent diabetes mellitus (IDDM) patients, 51 adult-onset IDDM patients, and 85 normal control subjects, and assessed the associations among these BAT2 alleles, TNFa microsatellite alleles (TNFa), and HLA-DRB1 alleles. The frequency of the BAT2.9 allele was significantly increased in the young-onset IDDM patients (12.8 vs 4.1%, Pc=0.04896), whereas the frequency of BAT2.12 allele was significantly decreased in young-onset IDDM patients (0.0 vs 11.8%, Pc=0.00002) compared with control subjects. The BAT2.9 allele was strongly associated with TNFa9 in the young-onset IDDM patients, although no association was found between the BAT2.9 and HLA-DRB1 alleles. The BAT2.12 allele was strongly associated with TNFa13, and with DRB1*1502 in control subjects. These results suggest that the BAT2 microsatellite polymorphism is associated with the age-at-onset of IDDM and possibly with the inflammatory process of pancreatic beta-cell destruction during the development of IDDM. However, this association is not independent of TNFa polymorphisms.

Adolescent↗
PubMed1999

Influence of TNF microsatellite polymorphisms (TNFa) on age-at-onset of insulin-dependent diabetes mellitus.

The TNF-alpha gene is located in the HLA region and has been implicated in the pathogenesis of Type I (insulin-dependent) diabetes mellitus (IDDM). We investigated the frequency of TNFa microsatellite alleles in 76 young-onset IDDM patients, 65 adult-onset IDDM patients, and 90 control subjects. We also examined the association of these TNFa alleles with HLA-DRB1 alleles, HLA-class I alleles, and TNF-alpha production. The frequency of the TNFa2 and TNFa9 alleles was increased in the young-onset IDDM patients compared to control subjects, but the increased frequency of TNFa2 was not significant after the correction for the number of comparisons was made. We did not find any association of TNFa2 or TNFa9 with any of the HLA-DRB1 alleles. In contrast, the frequency of the TNFa13 allele was decreased in both the young-onset and the adult-onset IDDM patients compared to the control subjects, but the difference lost significance after the correction was made in the adult-onset IDDM. The TNFa13 allele was strongly associated with DRB1*1502. Patients with TNFa2 or TNFa9 had greater TNF-alpha production, while those positive for TNFa13 had lower TNF-alpha production than patients with non-TNFa2, a9, and a13 alleles. These results suggest that TNFa polymorphisms are associated with age-at-onset of IDDM and influence the inflammatory process of pancreatic beta cell destruction in the development of IDDM.

Adolescent↗
PubMed1999

A Drosophila gene encoding multiple splice variants of Kazal-type serine protease inhibitor-like proteins with potential destinations of mitochondria, cytosol and the secretory pathway.

A Drosophila gene (KAZ1), mapped to cytological position 61A1-2 on chromosome 3, has been cloned and found to encode multiple splice variants of Kazal-type serine protease inhibitor-like proteins. KAZ1 consists of five exons and four alternatively retained introns to produce six transcripts of type AB, C1, C2, C3, D and E. The AB transcript contains two ORFs, of which the upstream one produces a polypeptide alpha, which has a mitochondrial sorting signal. Localization to mitochondria was confirmed by expression in COS1 cells. The downstream ORF is shared partially with type C1, C2, C3, D and E transcripts and produces polypeptides beta, gamma, delta and epsilon when expressed in Drosophila cells. Type C1, C2 and C3 transcripts differ only in the 5'-noncoding sequence and thus all produce type gamma. Polypeptides gamma and epsilon have a signal sequence at their N-termini and are secreted into the medium while beta and delta lack this sequence and remain in the cytoplasm. Isoforms beta and epsilon share a common C-terminal sequence distinct from that shared by polypeptides gamma and delta. The N-terminal sequences of isoforms beta to epsilon contain a PEST region which could induce rapid intracellular degradation of isoforms beta and delta. Sequence analysis of the Kazal-type domain suggests a similar folding pattern as observed for rhodniin and SPARC/BM-40. Northern analysis and in situ hybridization showed that the type C3 transcript is predominant and the expression is highest in midgut at larval stage.

Amino Acid Sequence↗
PubMed1999

Brachyury (T) expression in embryonal carcinoma P19 cells resembles its expression in primitive streak and tail-bud but not that in notochord.

Brachyury (T) is involved in mesoderm induction during early mouse development. T expression in embryonal carcinoma P19 cells, which differentiate into mesoderm derivatives in vitro, was studied. Endogenous T expression in P19 cells was transiently induced when the cells were allowed to form aggregates. This expression was enhanced by dimethyl sulfoxide. In situ hybridization showed that T expressing cells formed clusters on the aggregates. Transfection of plasmids encoding reporter genes under the control of the upstream region of T showed that the sequence up to -351 bp can resemble the differentiation-dependent expression of T in P19 cells. To define the promoter region regulating T expression, transgenic mice carrying LacZ under the control of the upstream region were prepared. The region up to -351 bp is sufficient to direct the expression in the primitive streak and tail-bud. The upstream region up to -2400 bp does not support expression in the notochord. The sequence between -987 and -585 bp enhances expression in the primitive streak and tail-bud. In the tail-bud where new cells for elongation of the anteroposterior axis were continuously supplied, the sequence up to -987 bp drove lacZ expression in gut endoderm and prospective neuroectoderm as well as in mesoderm derivatives.

Animals↗
PubMed1999

Cholestatic jaundice in two patients with primary amyloidosis: ultrastructural findings of the liver.

Two patients with primary amyloidosis (amyloid light chain case) and severe cholestatic jaundice are described. Liver biopsy in the preterminal stage demonstrated amyloid deposits in the perisinusoidal space and in portal tracts, and hepatocytes were atrophic because of compression by amyloid fibrils. Ultrastructural findings showed amyloid fibrils not only in Disse's space but also in the sinusoids, and the hepatocyte microvilli facing the amyloid fibrils were spicular. There were aggregates of lysosomal granules in the vicinity of bile canaliculi and some bile canaliculi were dilated with loss of microvilli. Amyloid fibrils in the portal tract compressed bile ductules, causing wide intercellular space and separated basement membranes from their epitheliums. These findings suggested disturbance in transporting not only of essential materials from sinusoids to hepatocytes but also of secretory vesicles into bile canaliculi and leakage of bile juice from small bile ductules in preterminal stage of primary amyloidosis.

Aged↗
PubMed1999

Expression of messenger RNAs for membrane-type 1, 2, and 3 matrix metalloproteinases in human renal cell carcinomas.

PURPOSE: Three different membrane-type matrix metalloproteinases (MT1, 2, and 3-MMP) that can activate proMMP-2 (progelatinase A) are thought to play an important role in invasion and metastasis by various human carcinomas. To further clarify this role, we examined mRNA expression of MT-MMPs in human renal cell carcinomas. MATERIALS AND METHODS: mRNA was extracted from 25 clinical specimens of renal cell carcinoma and 23 specimens of normal renal parenchyma remote from the tumor. Reverse transcription polymerase chain reaction (RT-PCR) using specific primers was performed, and PCR products were hybridized to 32P-labeled internal probes and analyzed by a bioimage analyzer. RESULTS: MT1, 2, and 3-MMP mRNA expression in carcinomas was significantly higher than in normal parenchyma. In terms of the pathologic stage, MT1-MMP mRNA expression in pT2 and pT3 tumors was significantly higher than those in pT1 tumors. Although the sample size was small, it was evident that MT3-MMP mRNA expression in clear cell subtype renal cell carcinomas was higher than in the group of tumors including the granular cell subtype. CONCLUSIONS: These three MT-MMPs may play an important role in the pathogenesis of human renal cell carcinoma, and MT1-MMP in particular is important in invasion by carcinoma cells. It is interesting that the expression of MT3-MMP was higher in carcinomas, especially clear cell carcinoma, than in normal parenchyma, so that MT3-MMP may provide a clue an understanding of the molecular mechanism of carcinogenesis in human kidney.

Carcinoma, Renal Cell↗